Is Ritalin As Effective--And As Harmless--As It Could Be?

DALLAS, March 29 -- Ritalin, the treatment of choice for an estimated 2 million or more children suffering from attention deficit hyperactivity disorder, could be more effective and cause fewer side-effects if it were administered as a single compound rather than as a mixture, say chemists at Brookhaven National Laboratory. Yu-Shin Ding, Ph.D., and colleagues presented their findings here today at the national meeting of the American Chemical Society, world's largest scientific society.

Methylphenidate (marketed as Ritalin) is a chiral drug, meaning that it comes in two molecular forms, one a mirror image of the other (enantiomers). Currently Ritalin, which topped $350 million in sales last year, said Ding, is distributed as a "racemic" mixture of both its chiral molecules -- d-threo and l-threo.

However, some evidence has suggested that the drug's therapeutic effect resides solely in the d-threo enantiomer, which is about 10 times more potent than its chiral counterpart, according to Ding. "If the beneficial effects of the drug reside only in the d-threo form," she said, "then fifty percent of the weight of the administered drug may not contribute to its therapeutic effects."

Ding, along with colleagues Joanna S. Fowler and Nora Volkow, studied the individual effects of d-threo and l-threo on the central nervous system. They tagged each enantiomer with a short-lived radioactive tracer chemical -- calleda carbon-11 isotope -- with a half-life of 20 minutes. They then used positron emission tomography (PET) to compare the enantiomers' effects in the brains of baboons and humans. (Radiotracers emit signals as they decay that can be collected by a PET scan to generate images.) The study showed that the d-threo enantiomer bound precisely to the dopamine targets in the brain, while the binding of l-threo was mostly non-specific.

What's more, Ding says, the l-threo enantiomer may ha

Contact: Jim Bohning
American Chemical Society

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